IGF-1 is a single chain polypeptide consisting of 70 amino-acid residues with three disulfide bridges. It may exert physiological effects via endocrine, autocrine, or paracrine pathways. IGF-1 is normally present in the blood and is usually complexed with binding proteins. The availability of IGF-1 in the bloodstream is regulated by at least six of these binding proteins. Some binding proteins inhibit IGF-1 activity while others increase it. Some of the binding proteins protect IGF-1 and greatly extend its serum half-life. Normally IGF-1 exits the circulation by crossing the endothelium to reach its target tissues and interact with their cell surface receptors. IGF-1 is the principal hormonal mediator of statural growth during childhood.
This small polypeptide hormone is also a known mitogen and plays a significant role in embryogenesis and early growth, carcinogenesis, hypertrophy and has anti-apoptotic activities. The IGF-1 receptor, which is a mediator of IGF-1's intracellular proliferative signaling, is over-expressed in many cancer cells. Epidemiological studies have linked high IGF-1 levels in the blood to several cancers including colorectal, prostate, uterine, bladder, ovarian and breast cancer. The Physicians' Health Study, for example, has indicated a strong association between circulating IGF-1 levels and the subsequent occurrence of prostate cancer (J M Chan, et al., J Natl Cancer Inst 94:1099-106 (2002); J M Chan, et al., Science 279: 451-566 (1998).
IGF-1 has at least two effects on cancer cells that lead to their uncontrolled proliferation. IGF-1, via multiple cellular signaling pathways, stimulates the synthesis of both DNA and protein. Moreover, IGF-1 signaling simultaneously inhibits apoptosis, thereby increasing cancer cell survival. In combination, these two effects can have a profound influence on carcinogenesis.
Higher cell proliferation rates increase the chance that a genetically damaged cell will divide to reach a critical mass and/or undergo a second transforming genetic mutation. Suppression of apoptosis aggravates the situation since this natural screening process can no longer eliminate damaged cells. If accumulative cellular damage precedes carcinogenesis, as the age relatedness of cancer would suggest, then minor alterations early in its progression could produce major consequences in the final outcome. Additionally, it is thought that IGF-1, as a result of its direct functions, may play a role in determining the longevity of an organism. In this regard, the longevity field provides research studies that indicate reduced IGF-1 signaling may be important in lifespan extension.
Thus, what is needed is a simple and method of increasing longevity and preventing cancer development and recurrence or growth by selectively modulating IGF-1 levels in the body.